Using Genetic Tools to Dissect Neural Circuits for Social Communication

项目摘要 无法形成和维持社会纽带是一系列神经精神病学和 神经发育障碍。这些社会缺陷在很大程度上源于表达能力和接受能力的受损 发声沟通技巧。令人惊讶的是，语音交流如何促进社会联系并不是 这很好理解，部分原因是潜在的神经回路仍然没有得到很好的描述。在这里，我们建议使用 使用一种新的遗传方法选择性地标记在社交相遇期间活跃的神经元 发声。我们将把这种创新的方法与活体成像、电生理学、化学和 神经活动的光遗传扰动，以及识别神经回路的行为测量 促进发声交流的表现力和接受性，为社会联系服务。在目标1中， 我们将测试这样一种想法，即中脑导水管周围灰质(PAG)中特定的神经元亚群是 雄性和雌性小鼠在它们的社会互动中发出声音所需的。在目标2中，我们 将操纵这些PAG神经元的活动来抑制或增强发声，从而使我们能够测试 认为这些发声能促进社会联系的想法。在目标3中，我们将测试前额叶皮质 为PAG发声神经元提供输入的PFC神经元在调节发声过程中起着重要作用。 社会语境的作用。在目标4中，我们将可逆地使PFC神经元静音或成像，这些神经元向 PAG测试他们在男性和女性中产生附属社会反应的作用这一想法 听一个发声的人说话。这些研究将确定控制发声的神经元和电路。 在社会相遇期间，并促进社会联系，以响应这些声音信号。这项研究将 也为将来的研究奠定了基础，这些研究探索了这些电路在小鼠模型中是如何受到影响的 神经精神障碍，以社交和联系障碍为特征，如自闭症 谱系障碍和精神分裂症。

Project Summary An inability to form and maintain social bonds typifies a wide range of neuropsychiatric and neurodevelopmental disorders. These social deficits stem in large part from impaired expressive and receptive vocal communication skills. Surprisingly, exactly how vocal communication promotes social affiliation is not well understood, in part because the underlying neural circuits remain poorly described. Here we propose the use of a novel genetic approach to selectively tag neurons that are active during social encounters that elicit vocalizations. We will combine this innovative method with in vivo imaging, electrophysiology, chemical and optogenetic perturbations of neural activity, and behavioral measurements to identify neural circuits that facilitate expressive and receptive aspects of vocal communication in the service of social affiliation. In Aim 1, we will test the idea that a specific subpopulation of neurons in the midbrain periaqueductal gray (PAG) is required for male and female mice to produce vocalizations used during their social interactions. In Aim 2, we will manipulate the activity of these PAG neurons to suppress or augment vocalization, allowing us to test the idea that these vocalizations promote social affiliation. In Aim 3, we will test the idea that prefrontal cortical (PFC) neurons that provide input to PAG vocalization neurons are important in regulating vocalization as a function of social context. In Aim 4, we will either reversibly silence or image PFC neurons that provide input to the PAG to test the idea that they play a role in generating affiliative social responses in males and females listening to a vocalizing individual. These studies will identify the neurons and circuits that gate vocalization during social encounters and promote social affiliation in response to these acoustic signals. This research will also build the foundation for future studies that explore how these circuits are affected in mouse models of neuropsychiatric disorders characterized by social communication and affiliation deficits, such as autism spectrum disorder and schizophrenia.